PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers
Squibb Company (NYSE: BMY) today announced that the U.S. Food and
Drug Administration (FDA) approved YERVOY™ (ipilimumab) 3 mg/kg for the
treatment of patients with unresectable (inoperable) or metastatic
melanoma. YERVOY is the first and only therapy for unresectable or
metastatic melanoma to demonstrate a significant improvement in overall
survival based on results from a pivotal randomized, double-blind Phase
3 study. Median overall survival was 10 months (95% CI: 8.0-13.8) for
YERVOY, 6 months (95% CI: 5.5-8.7) for gp100 and 10 months (95% CI:
8.5-11.5) for YERVOY + gp100, with p-values of 0.0026 (not adjusted for
multiple comparisons) for YERVOY and 0.0004 for YERVOY + gp100 vs.
gp100, respectively. As published in the New England Journal of
Medicine, the Kaplan-Meier estimated survival rate at 1 year was 46%
(95% CI: 37.0, 54.1) in the YERVOY armvs. 25% (95% CI: 18.1,
32.9) in the gp100 arm. The estimated survival rate at 2 years was 24%
(95% CI: 16.0, 31.5) in the YERVOY arm vs. 14%2 (95% CI: 8.0,
20.0) in the gp100 arm. YERVOY, which is a recombinant, human monoclonal
antibody, is the first FDA-approved cancer immunotherapy that blocks the
cytotoxic T- lymphocyte antigen-4 (CTLA-4).

The full Prescribing Information for YERVOY includes a boxed warning for
immune-mediated adverse reactions. YERVOY can result in severe and fatal
immune-mediated adverse reactions due to T-cell activation and
proliferation. These immune-mediated reactions may involve any organ
system; however, the most common severe immune-mediated adverse
reactions are enterocolitis, hepatitis, dermatitis (including toxic
epidermal necrolysis), neuropathy, and endocrinopathy. The majority of
these immune-mediated reactions initially manifested during treatment;
however, a minority occurred weeks to months after discontinuation of
YERVOY (ipilimumab). Permanently discontinue YERVOY and initiate
systemic high-dose corticosteroid therapy for severe immune-mediated
reactions. Patients should be assessed for signs and symptoms of
enterocolitis, dermatitis, neuropathy and endocrinopathy and clinical
chemistries should be evaluated, including liver function tests and
thyroid function tests, at baseline and before each dose. Please see
complete Important Safety Information including Boxed WARNING regarding
immune-mediated adverse reactions on pages 6-9.

“Metastatic melanoma is one of the most aggressive forms of cancer and
despite the rising incidence,no new treatments have been
approved in more than a decade,” said Lamberto Andreotti, chief
executive officer, Bristol-Myers Squibb. “Today’s approval of YERVOY is
an example of Bristol-Myers Squibb living its mission of developing and
delivering innovative medicines that address the unmet needs of patients
with serious diseases. It also represents a significant step forward in
our commitment to deliver and execute against our differentiated and
focused BioPharma strategy.”

“For the first time, oncologists have a treatment option for patients
with unresectable or metastatic melanoma that has been proven in a
randomized Phase 3 clinical trial to significantly extend the lives of
patients,” said Steven J. O’Day, M.D., Chief of Research and Director of
the Melanoma Program at The Angeles Clinic and Research Institute,
California, and an investigator of the pivotal trial. “In fact, the
Kaplan-Meier curve from this study suggests a prolonged survival benefit
for some patients.” Median overall survival was 10 months (95% CI:
8.0-13.8) for YERVOY (ipilimumab), 6 months (95% CI: 5.5-8.7) for gp100
and 10 months (95% CI: 8.5-11.5) for YERVOY + gp100, with p-values of
0.0026 (not adjusted for multiple comparisons) for YERVOY and 0.0004 for
YERVOY + gp100 vs gp100, respectively.

“The FDA approval of YERVOY is the culmination of more than 14 years of
research and development by our dedicated development teams and clinical
trial investigators,” said Elliott Sigal, M.D., Ph.D., executive vice
president, chief scientific officer, and president, Research &
Development, Bristol-Myers Squibb. “YERVOY is the first FDA-approved
compound from our robust immuno-oncology pipeline, which comprises a
variety of other compounds with the potential to harness the patient’s
immune system to fight cancer.” The mechanism of action of ipilimumab’s
effect in patients with melanoma is indirect, possibly through T-cell
mediated anti-tumor immune responses.

Bristol-Myers Squibb has agreed with the FDA to conduct a post-marketing
study comparing the safety and efficacy of the 3 mg/kg dose vs. an
investigational 10 mg/kg dose in patients with unresectable or
metastatic melanoma.

The company expects to begin shipping YERVOY within weeks of today’s FDA
approval.

Overall Survival and Safety Profile of YERVOY in Patients with
Unresectable or Metastatic Melanoma

YERVOY is the first and only therapy to demonstrate a statistically
significant overall survival benefit in patients with unresectable or
metastatic melanoma. The approval is based on a Phase 3, randomized
(3:1:1), double-blind study that included 676 patients with unresectable
or metastatic melanoma who were previously treated with one or more of
the following: aldesleukin, dacarbazine, temozolomide, fotemustine, or
carboplatin.

As published in the New England Journal of Medicine, the
Kaplan-Meier estimated survival rate at 1 year was 46% (95% CI: 37.0,
54.1) in the YERVOY armvs. 25% (95% CI: 18.1, 32.9) in the
gp100 arm. The estimated survival rate at 2 years was 24% (95% CI: 16.0,
31.5) in the YERVOY arm vs. 14%2 (95% CI: 8.0, 20.0) in the
gp100 arm. Patients treated with YERVOY had a 34% reduction in the risk
of death over the gp100 control arm (HR = 0.66 [95% CI: 0.51-0.87],
P=0.0026). Patients treated with YERVOY (ipilimumab) plus gp100 had a
32% reduction in the risk of death over the gp100 control arm (HR = 0.68
[95% CI: 0.55-0.85], P=0.0004). Median overall survival was 10 (95% CI:
8.0-13.8), 10 (95% CI: 8.5-11.5) and 6 (95% CI: 5.5-8.7) months for the
YERVOY alone, YERVOY + gp100 arm and gp100 alone arms, respectively.

The best overall response rate (BORR) as assessed by the investigator
was 10.9% (95% CI: 6.3, 17.4) in patients treated with YERVOY
(ipilimumab) (n=15 of 137), 5.7% (95% CI: 3.7, 8.4) in the YERVOY +
gp100 arm (n=23 of 403) and 1.5% (95% CI: 0.2, 5.2) in the gp100 arm
(n=2 of 136). BORR is defined as the total number of patients with the
best response of a complete response (CR) or a partial response (PR)
divided by the total number of patients treated. The median duration of
response was 11.5 months in the YERVOY + gp100 arm and has not been
reached in the YERVOY or gp100 arm at the time of the analysis because
more than half of patients who had a confirmed CR or PR remained free of
any relapse.

Results from this study were previously published in the New England
Journal of Medicine and presented during a plenary session at the
46th Annual Meeting of the American Society of Clinical Oncology.

YERVOY: Risk Evaluation and Mitigation Strategy

“Bristol-Myers Squibb is committed to the safe and appropriate use of
our medicines,” said Annalisa Jenkins, senior vice president global
medical, Bristol-Myers Squibb. “As part of the U.S. approval of YERVOY,
we have collaborated with the FDA on the development of a Risk
Evaluation and Mitigation Strategy to help inform patients and providers
about important safety risks associated with YERVOY.”

The YERVOY Risk Evaluation and Mitigation Strategy (REMS) consists of a
Communication Plan to inform potential prescribers and supportive
healthcare providers about serious adverse reactions associated with
YERVOY. To support this communication plan, Bristol-Myers Squibb has put
in place a system that will enable the company to deliver these
educational materials to the appropriate healthcare professional at the
time of product order.

More information and downloadable safety education materials will be
available at www.YERVOY.com.

YERVOY Was Studied in a Pivotal Phase 3 Clinical Trial of Patients
with Unresectable or Metastatic Melanoma

The approval is based on a Phase 3, double-blind study that randomized
676 patients with unresectable or metastatic melanoma who were
previously treated with one or more of the following: aldesleukin,
dacarbazine, temozolomide, fotemustine, or carboplatin.Patients
were randomized in a 3:1:1 ratio to receive either YERVOY (ipilimumab)
(3mg/kg) in combination with the investigational peptide vaccine gp100
(n=403), YERVOY alone (3mg/kg; n=137), or gp100 alone (n=136).

The primary endpoint of the pivotal Phase 3 study was overall survival
in the YERVOY plus gp100 arm vs. the gp100 arm. Secondary efficacy
endpoints included overall survival in the YERVOY plus gp100 arm vs. the
YERVOY arm, overall survival in the YERVOY arm vs. the gp100 arm, BORR
at week 24 and duration of response.

Patients received YERVOY (3mg/kg) as an intravenous infusion
administered over 90 minutes every 3 weeks for four doses. Assessment of
tumor response to YERVOY was conducted at weeks 12 and 24, and every 3
months thereafter. Patients with evidence of objective tumor response at
12 or 24 weeks had assessment for confirmation of durability of response
at 16 or 28 weeks, respectively. Between 57% and 64% of patients treated
in each study arm received all four planned doses.

YERVOY was studied in patients with a typically poor prognosis,
including those with brain metastases, elevated LDH, and visceral
disease (M1c). In the study, 71% had M1c stage, 12% had a history of
previously-treated brain metastasis, 98% had ECOG performance status of
0 and 1, 23% had received aldeskeukin and 38% had elevated LDH level.
Additionally, 29% of patients were 65 years or older with a median age
of 57 years.The median duration of follow-up was 8.9 months.
Please see complete Important Safety Information including Boxed WARNING
regarding immune-mediated adverse reactions on pages 6-9.

YERVOY: Mechanism of Action

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a negative regulator of
T-cell activation.Ipilimumab binds to CTLA-4 and blocks the
interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4
has been shown to augment T-cell activation and proliferation. The
mechanism of action of ipilimumab’s effect in patients with melanoma is
indirect, possibly through T-cell mediated anti-tumor immune responses.

About the YERVOY Filing

YERVOY (ipilimumab) was granted orphan drug status in 2004, which is a
designation given to drugs that treat rare diseases. In 2006, YERVOY
received a fast track designation. The FDA’s fast track process is
designed to facilitate the development, and expedite the review, of
drugs to treat serious diseases and fill an unmet medical need. The
purpose is to get important new drugs to the patient earlier. In August
of 2010, YERVOY received a priority review designation, which is given
to drugs that offer major advances in treatment, or provide a treatment
where no adequate therapy exists.

Metastatic Melanoma is the Deadliest Form of Skin Cancer

Melanoma is a form of skin cancer characterized by the uncontrolled
growth of pigment-producing cells (melanocytes) located in the skin.
Metastatic melanoma is the deadliest form of the disease, and occurs
when cancer spreads beyond the surface of the skin to other organs, such
as the lymph nodes, lungs, brain or other areas of the body. Some cancer
cells can actively evade surveillance by the immune system, allowing
tumors to survive. Melanoma is mostly curable when treated in its early
stages. However, in its late stages, the average survival rate is just 6
months with a 1-year mortality rate of 75%, making it one of the most
aggressive forms of cancer. These rates are based on a meta-analysis of
42 Phase 2 trials of more than 2,100 previously-treated and
treatment-naïve patients with Stage IV metastatic melanoma conducted by
multiple cooperative groups from 1975-2005.

“Metastatic melanoma is a devastating disease and treating it has been a
significant challenge,” said Tim Turnham, executive director of the
Melanoma Research Foundation. “The incidence of melanoma has been
increasing for at least 30 years. The median age at diagnosis for
melanoma is 57 and the median age at death is 67.”

About Bristol-Myers Squibb’s Patient Access Programs

Bristol-Myers Squibb is committed to supporting patient access to YERVOY
and has put in place a number of programs to help patients and
providers. Destination Access™, which is the Bristol-Myers Squibb
Reimbursement Support Program, is a comprehensive service that supports
patient access by providing benefits investigation support, prior
authorization assistance, appeals assistance and patient assistance.
More information about our patient assistance program can be obtained by
calling 1-800-861-0048.

In addition to Destination Access, Bristol-Myers Squibb has developed
the YERVOY Co-Pay Program to help eligible, commercially insured
patients who have been prescribed YERVOY for unresectable or metastatic
melanoma with their co-pay or co-insurance costs for this drug.
Additional information about this program will be available at www.YERVOY.com.

Important Safety Information

WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS

YERVOY can result in severe and fatal immune-mediated adverse
reactions due to T-cell activation and proliferation. These
immune-mediated reactions may involve any organ system; however, the
most common severe immune-mediated adverse reactions are enterocolitis,
hepatitis, dermatitis (including toxic epidermal necrolysis),
neuropathy, and endocrinopathy. The majority of these immune-mediated
reactions initially manifested during treatment; however, a minority
occurred weeks to months after discontinuation of YERVOY.

Assess patients for signs and symptoms of enterocolitis, dermatitis,
neuropathy and endocrinopathy and evaluate clinical chemistries
including liver function tests (LFTs) and thyroid function tests at
baseline and before each dose.

Across all YERVOY-treated patients (n=511), 5 (1%) developed
intestinal perforation, 4 (0.8%) died as a result of complications,
and 26 (5%) were hospitalized for severe enterocolitis.

Monitor patients for signs and symptoms of enterocolitis (such as
diarrhea, abdominal pain, mucus or blood in stool, with or without
fever) and of bowel perforation (such as peritoneal signs and ileus).

In symptomatic patients, rule out infectious etiologies and
consider endoscopic evaluation for persistent or severe symptoms.

Immune-mediated Hepatitis:

In the pivotal Phase 3 study in YERVOY-treated patients, severe,
life-threatening, or fatal hepatotoxicity (AST or ALT elevations >5X
the upper limit of normal (ULN) or total bilirubin elevations >3X the
ULN; Grade 3–5) occurred in 8 (2%), with fatal hepatic failure
in 0.2% and hospitalization in 0.4%.

Patients may present with fatigue, headache, mental status
changes, abdominal pain, unusual bowel habits, and hypotension, or
nonspecific symptoms which may resemble other causes such as brain
metastasis or underlying disease.

Unless an alternate etiology has been identified, signs or
symptoms of endocrinopathies should be considered immune-mediated.

Monitor thyroid function tests and clinical chemistries at the
start of treatment, before each dose, and as clinically indicated
based on symptoms.

In a limited number of patients, hypophysitis was diagnosed by
imaging studies through enlargement of the pituitary gland.

YERVOY is classified as pregnancy category C. There are no adequate
and well-controlled studies of YERVOY in pregnant women. Use YERVOY
during pregnancy only if the potential benefit justifies the potential
risk to the fetus.

Human IgG1 is known to cross the placental barrier and YERVOY is an
IgG1; therefore, YERVOY has the potential to be transmitted from the
mother to the developing fetus.

It is not known whether YERVOY is secreted in human milk. Because many
drugs are secreted in human milk and because of the potential for
serious adverse reactions in nursing infants from YERVOY, a decision
should be made whether to discontinue nursing or to discontinue YERVOY.

Common Adverse Reactions:

The most common adverse reactions (≥5%) in patients who received
YERVOY at 3 mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%),
rash (29%), and colitis (8%).

Please see full Prescribing Information, including Boxed Warnings
regarding Immune-related side effects at www.YERVOY.com
or www.bms.com.

Immuno-Oncology at Bristol-Myers Squibb

Immuno-oncology, which focuses on the scientific potential of harnessing
the unique properties of the immune system to fight cancer, is a key
area of focus at Bristol-Myers Squibb. A variety of compounds and
immunotherapeutic approaches are being explored for patients with
different types of cancer. The substantial potential of the immune
system’s intrinsic ability to fight cancer is fundamental to the
immuno-oncology research at Bristol-Myers Squibb and its ongoing
commitment to shaping and advancing cancer care. The mechanism of action
of ipilimumab’s effect in patients with melanoma is indirect, possibly
through T-cell mediated anti-tumor immune responses.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission
is to discover, develop and deliver innovative medicines that help
patients prevail over serious diseases. For more information about
Bristol-Myers Squibb, visit www.bms.com,
or follow us on Twitter at http://twitter.com/bmsnews.

This press release contains "forward-looking statements" as that term
is defined in the Private Securities Litigation Reform Act of 1995
regarding product development. Such forward-looking statements are based
on current expectations and involve inherent risks and uncertainties,
including factors that could delay, divert or change any of them, and
could cause actual outcomes and results to differ materially from
current expectations. No forward-looking statement can be guaranteed.
Among other risks, there can be no guarantee that ipilimumab will become
a commercially successful product. Forward-looking statements in this
press release should be evaluated together with the many uncertainties
that affect Bristol-Myers Squibb's business, particularly those
identified in the cautionary factors discussion in Bristol-Myers
Squibb's Annual Report on Form 10-K for the year ended December 31,
2010, in our Quarterly Reports on Form 10-Q and our Current Reports on
Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly
update any forward-looking statement, whether as a result of new
information, future events or otherwise.